An interdisciplinary team at the USC Center for Personalized Brain Health (CPBH) is targeting a family of enzymes that can increase the risk of inflammation in the brains of people with the APOE4 gene variation-the most significant genetic risk factor for late-onset Alzheimer’s-as a way to prevent the disease.
By activating or inhibiting the enzymes, the scientists, led by CPBH director Hussein Yassine, MD, have succeeded in identifying a promising pathway to turn off brain inflammation before it does its damage.
Now joining the fight is the Norman and Mary Pattiz Foundation, with a $3 million gift to the Keck School of Medicine of USC that will support promising research, including novel drug discovery and other efforts aimed at early detection and prevention of Alzheimer’s.
The future in motion
The newly created Norman and Mary Pattiz Alzheimer’s Research Fund will provide pilot funding and accelerate priority projects of the USC Alzheimer’s Disease Research Center (ADRC). In addition to drug targeting, which includes imaging modality development, and the use of artificial intelligence to pinpoint small molecules involved in brain inflammation, the fund will also support efforts to modernize the center’s brain pathology library and look at brain inflammation markers in patients with Alzheimer’s.
Also made possible by the funding will be a plan to create a registry for early detection of individuals at high risk for neuro-inflammation based on the APOE4 genetic variant and cardiovascular risk factors.
“We are extremely grateful to the Norman and Mary Pattiz Foundation for having the foresight to support research that is breaking new ground,” said Helena Chang Chui, MD, director of the ADRC and the Raymond and Betty McCarron Professor of Neurology. “That willingness to explore bold hypotheses is what has helped us to make headway in neurodegenerative diseases over the last several years.”
“Norman and Mary Pattiz were trailblazers in their respective careers, and we hope to honor their legacy by carrying that same spirit of innovation and determination into the fight against Alzheimer’s disease,” said Karen Kerrigan, Pattiz Foundation Board President and Norman Pattiz’s former business manager.
Other members of the Foundation Board are three long-time friends and colleagues of Norman Pattiz-Larry Freeman, Paul Krasnow, and Jeff Hershberg. “Each of our Board members has had personal experience with a loved one being impacted by Alzheimer’s disease,” said Freeman, a longtime USC supporter. “We feel certain Norman and Mary would be excited about the potential impact this gift can have in the quest for solutions to this devastating disease.”
The Norman and Mary Pattiz Alzheimer’s Research Fund will recruit APOE4 carriers through USC ARDC’s GeneScreen, an Alzheimer’s prevention registry focused on identifying genetic risk, and CPBH SPARK, a registry focused on understanding how lifestyle and health influences brain aging and the risk of Alzheimer’s disease.
Searching for clues
The Foundation support also establishes the Norman and Mary Pattiz Foundation Endowed Associate Professorship in Neuropathology, which extends the critical work of neuropathology within the ADRC research endeavors.
The inaugural holder is Anne Hiniker, MD, PhD, director of the USC ADRC Neuropathology Core, where researchers look for signs of disease and disease progression and how changes in the brain may relate to protein accumulations found in Alzheimer’s disease.
The Pattiz Foundation funding will provide Dr. Hiniker with protected research time to speed the capture of inflammation markers or signposts in the more than 1,100 brain tissue samples in the USC ADRC Neuropathology Core.
I am honored to serve as the inaugural Pattiz Endowed Associate Professor. We hope to do justice to the legacy of Norman and Mary Pattiz with ambitious work designed to set the stage for new therapies for Alzheimer’s disease.”
Dr. Anne Hiniker, MD, PhD, director of the USC ADRC Neuropathology Core
Two creative donors
An American broadcasting entrepreneur, Norman Pattiz founded Westwood One, a radio syndication company, in 1976. It became the nation’s largest radio network and a major global media company-leading to Pattiz’s induction into the National Radio Hall of Fame.
Norman Pattiz supported causes he cared deeply about, such as communications, education, and sciences. He served on the Board of Regents of the University of California, as well as the boards of USC Annenberg School for Communication and Journalism, Lawrence Livermore National Laboratory, and the Broadcasting Board of Governors of the United States of America.
Mary Turner Pattiz had her own impressive career as the silky on-air voice of the 1970s and ’80s rock ‘n’ roll era who was known on air as “The Burner, Mary Turner”. As a popular disc jockey, she was credited as part of the soundtrack of that era’s music and was often hailed as the “First Lady of Rock Radio” in Los Angeles. In 2023, Mary received a Legends induction into the Radio Hall of Fame.
She left her career in radio to earn her PhD in clinical psychology and became a certified substance abuse counselor. In 2010, she was elected chair of the Betty Ford Center in Rancho Mirage, California. She was the first non-Ford family member to chair the Center and later oversaw its merger with the Hazelden Foundation in 2013. She remained a Board member of the newly formed Hazelden Betty Ford Foundation for several more years.
Norman and Mary Pattiz passed away in 2022 and 2023, respectively, leaving in place a Board of Directors they entrusted to nurture causes that have meaning in people’s lives. The Board previously funded an endowed chair in ovarian cancer research at the USC Norris Comprehensive Cancer Center. Its latest gift solidifies a significant imprint for the foundation’s legacy within the Keck Medicine of USC ecosystem.
Focusing on brain health
The APOE gene is a risk factor but not a guarantee of developing Alzheimer’s disease. In one CPBH study of differences in APOE4 carriers, Dr. Yassine’s team found that people with elevated levels of the enzyme “calcium-dependent phospholipase A2” or cPLA2 developed dementia.
With his collaborators, Dr. Yassine then identified possible drug therapies to selectively target cPLA2, while protecting normal cellular function from adverse effects.
The team wants to expand on that important discovery to find other targets that also trigger neuroinflammation, with potential for developing new drugs for Alzheimer’s.
“Our goal is to determine whether these possible targets and treatment pathways are safe, feasible, and ultimately meaningful for human disease,” said Dr. Yassine.
“Thanks to the generosity of the Norman and Mary Pattiz Foundation, we have a better chance of pursuing these critical questions,” he added, “and finding the answers that can lead us forward.”
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